Recovery Improved in Covert Stroke With Exercise (RISE-2)

Silent ischemic, also known as "covert stroke vascular disease" (CSVD), contributes to neurological deficits that are caused by damage to small blood vessels in the brain. CSVD occurs six to ten times more often that an acute stroke. It is misleading to think, however, that CSVD is an inevitable part of "getting old" because people with CSVD are at high risk of developing an acute stroke or dementia. In fact, people with more CSVD lesion volume are more likely to develop day to day problems in planning, decision-making and speed of thinking. Unfortunately, there are no proven therapies designed to address CSVD. We propose to test whether aerobic exercise is an intervention that can combat CSVD because the disease is fundamentally a blood flow problem that may be improved by aerobic exercise. We will recruit CSVD adults with moderate to severe lesion burden and use magnetic resonance imaging (MRI) to study the brain in terms of structure, perfusion and function. Participants will be randomly assigned to either our established aerobic exercise program or a control stretching program. Both groups will take part in lab exercise sessions, which are designed to monitor progress and assess adherence to the program. The duration and intensity of their exercise will increase as participants progress. We will use activity log books, phone calls and extra "booster" exercise sessions, as needed, to maximize retention and adherence. We aim to show that aerobic exercise increases cerebral blood flow (CBF) in frontal-subcortical grey matter, supports regional tissue growth, and improves cognitive function in CSVD adults with substantial risk of acute stroke and dementia. A positive outcome of this research will provide strong support for additional clinical trials aimed at sustaining cognition and maintaining independent living.

This group will perform the 'Exercise Program' for months 0 to 6, and will be unsupervised for months 7 to 12.

This group will perform the 'Stretching Program' for months 0 to 6, and the 'Exercise Program' for months 7 to 12.

The 'Stretching Program' will teach stretching for the upper and lower limbs, and the trunk, as well as breathing exercises for relaxation. Supervised group activities will be performed once per week (45 minutes) and self-directed stretching will be encouraged 4 days per week and monitored by an activity journal. The intensity of stretching and number of stretches will be progressed every 2 weeks. Heart rate and perceived exertion will be monitored. The program will last 6 months.

The 'Exercise Program' will prescribe specific aerobic exercise to the participants. Supervised group exercise will be performed once per week (60 minutes) and self-directed exercise will be encouraged 4 days per week and monitored by an activity journal. The initial walking prescription will be set at ~1.6 km and an intensity equivalent to the anaerobic threshold and/or 60% of peak oxygen uptake. Progressions will be made every 2 weeks, increasing distance to a maximum of 6.4 km and then increasing to a max intensity of 80% of peak oxygen uptake and/or max duration of 60 minutes. Heart rate and perceived exertion will be monitored. The program will last 6 months.

Inclusion Criteria: Covert stroke: white matter hyperintensities of presumed vascular origin Ability to walk for 10 minutes without assistance from another person Fluent in English Ability to consent Exclusion Criteria: Highly fit individuals exercising ≥ 150 minutes per week Dementia Multiple Sclerosis Disabling stroke (ischemic or hemorrhagic) Major concurrent illness (e.g. chronic obstructive lung disorder, current or metastatic cancer, chronic kidney disease) Major psychiatric illness (e.g. bipolar, schizophrenia, major depression) Contraindications to MRI scanning (e.g. claustrophobia, implants, prostheses, metallic fragments) Contraindications to exercise (participants must have medical clearance to exercise from their attending physician) Recent change in health status (e.g. hospitalization within past month)